Systemic administration of phenyl-N-tert-butylnitrone protects the retina from light damage.

PURPOSE: This study was conducted to test the hypothesis that phenyl-N-tert-butylnitrone (PBN), a spin-trapping agent known to cross the blood-brain barrier and protect the brain from ischemia-reperfusion injury, is incorporated into the retina after intraperitoneal injection and protects photoreceptor cells from the damaging effects of constant visible light. METHODS: Albino rats were injected intraperitoneally with PBN (aqueous solution) or water, or were not injected, and then were placed in constant light (2700 lux) for 24 hours. The incorporation of PBN into the retina was determined by high-performance liquid chromatography. Electroretinograms (ERGs) were recorded before light treatment and 1 and 15 days after the cessation of exposure to constant light. Eyes were taken for histology at each time point and outer nuclear layer (ONL) thickness determined. RESULTS: PBN was incorporated into the retina after intraperitoneal injection. Both control (water-injected and uninjected) groups exposed to constant light maintained only 28% of ONL thickness and 20% of retinal function, compared with the unexposed control group. In contrast, the PBN-treated animals maintained 80% of ONL thickness and exhibited 87% of retinal function. CONCLUSIONS: PBN protects the albino rat retina from the damaging effects of constant light stress. That light-induced and hereditary retinal degenerations share certain morphologic hallmarks and follow a similar apoptotic mechanism of degeneration raises the possibility of pharmacologic therapy for hereditary and environmentally induced neurodegenerative disorders.

Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract.

PURPOSE: To investigate the functional protective effect of a synthetic (dimethylthiourea, DMTU) and a natural antioxidant (Ginkgo biloba extract, EGb 761) against light-induced retinal degeneration. METHODS: Wistar rats were exposed for 24 hours to 1700-lux light after treatment with DMTU or EGb 761. Electroretinograms were recorded before and on day (D)1, D3, D8, D15, D22, and D29 after light exposure. The b-wave amplitude was plotted against log L (ganzfeld luminance), providing the b-wave sensitivity curve. The Naka-Rushton function fitted to the sensitivity curve enabled derivation of the parameters Bmax (saturated amplitude) and K (luminance-inducing Bmax/2). In addition, rats from each group were killed for retinal morphometric analyses. RESULTS: In the untreated group, light exposure caused collapse of the b-wave sensitivity curves. Bmax was reduced by 51% at D1 without subsequent recovery. K increased temporarily, reverting to normal values 8 days later. The outer nuclear layer thicknesses decreased markedly in the superior retina. In the treated groups, light exposure had a weaker effect on sensitivity curves. The values of Bmax were not significantly different from those in the unexposed-untreated group, although K increased temporarily. Retinal morphometry was preserved. CONCLUSIONS: Dimethylthiourea and EGb 761 afford functional protection against light-induced retinal damage.

Light-induced variations of retinal sensitivity in rats.

PURPOSE: ERG responses were measured as a function of Ganzfeld luminance to evaluate functional damage induced by light on rat retinas. METHODS: Wistar rats were exposed to a fluorescent light of 1700 lux for 12 h, 24 h, 48 h and 72 h. We recorded ERGs before and one night after exposure, then 3, 8, 15, 22 and 29 days later. The b- and PIII-wave amplitudes were plotted against luminance for each group at each recovery time. RESULTS: The retinal damage induced by a pupillary illuminance of 1700 lux ranged from low to severe as exposure duration increased from 12 h to 72 h, respectively. We observed an effect immediately after light exposure but no improvement during the recovery period. The b-wave amplitude was reduced by 40, 60, 80 and 90 percent after 12, 24, 48 and 72 h of light exposure, respectively; the PIII-wave amplitude was reduced by 30, 40, 70 and 90 percent after these respective exposures. The Ganzfeld luminance eliciting a 50 microV b-wave amplitude increased significantly with exposure duration, but the luminance eliciting the maximal b-wave amplitude was not dependent on this duration. Hence we suggest that the ERG decrease is due to a reduction in photoreceptor number. CONCLUSIONS: We present a full analysis of the electrophysiological parameters recorded from light-exposed or non-exposed rats. This model is a useful tool to study in vivo retinal degeneration.